The regulation and function of metallothioneins are being analyzed by molecular genetic and biochemical approaches in both mammalian cells and yeast. Human metallothionein genes exhibit cell-specific expression that can be altered by the ras oncogene. The specificity of expression is correlated with differential metal-binding properties of the proteins. Attempts are in progress to detect and isolate the cellular factors involved in regulation by heavy metals and other agents. A copper-inducible metallothionein-like protein of yeast has been demonstrated to serve two functions: copper detoxification and negative autoregulation of its own expression. Both functions are complemented by mammalian metallothionein demonstrating the functional analogy between the higher and lower eukaryotic systems.